The mitochondrial respiratory chain is responsible for the conversion of the chemical energy in the breakdown products of foodstuffs into chemiosmotic energy for use in ATP synthesis. There are four multicomponent complexes making up the respiratory chain, an NADH ubiquinone reductase (complex I), succinate ubiquinone reductase (complex II), ubiquinol cytochrome c oxidoreductase (complex III) and cytochrome c oxidase (complex IV). Cytochrome c oxidase is composed of a 9 different subunits in fungi such as the yeast Saccharomyces cerevisiae and 13 different subunits in mammals, 3 coded for on mtDNA and made in the mitochondrion, the remainder encoded in the nucleus. A low resolution structure of the mammalian enzyme has been obtained (25 Angstroms). Ongoing work is aimed at localizing subunits within this structure and determining the orientation of each subunit. Recent evidence indicates that several of the subunits of the mammalian cytochrome c oxidase are present as isoforms. Studies are proposed to characterize the isoforms of the enzyme complex in beef and in humans and to determine the tissue distribution of these forms. An analysis of the tissue specificity and developmental regulation of the isoforms of cytochrome c oxidase should greatly aid in understanding the molecular basis of a variety of human diseases due to dysfunction of this enzyme. Other projects proposed involve crystallization of cytochrome c oxidase using enzyme from a variety of sources and establishment of the molecular basis of cytochrome c oxidase deficiency in a case of Kern-Sayres syndrome, preliminary study on which suggest the defect involves splicing of the subunit IV transcript.